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JOURNAL ONKOLOGIE – STUDIE
ELECTRA

Study of Abemaciclib and Elacestrant in Patients With Brain Metastasis Due to ER+/HER-2- Breast Cancer

Rekrutierend

NCT-Nummer:
NCT05386108

Studienbeginn:
August 2022

Letztes Update:
06.08.2024

Wirkstoff:
Elacestrant, Abemaciclib

Indikation (Clinical Trials):
Neoplasms, Brain Neoplasms, Breast Neoplasms, Neoplasms by Site, Nervous System Neoplasms, Central Nervous System Neoplasms, Nervous System Diseases, Brain Diseases, Central Nervous System Diseases, Breast Diseases

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Stemline Therapeutics, Inc.

Collaborator:
-

Kontakt

Studienlocations
(3 von 59)

Clinic Worms gGmbH
67550 Worms
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
Klinikum Bayreuth GmbH
95445 Bayreuth
(Bayern)
GermanyRekrutierend» Google-Maps
Uniklinik Koeln - Klinik und Poliklinik fuer Frauenheilkunde
Cologne
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Universitatsklinikum Carl Gustav Carus
Dresden
(Sachsen)
GermanyRekrutierend» Google-Maps
Universitaetsklinikum Duesseldorf
Düsseldorf
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Hautkrebszentrum Universitätsklinikum Erlangen
Ulmenweg 18
91054 Erlangen
(Bayern)
DeutschlandRekrutierend» Google-Maps
Clinic Worms gGmbH
67550 Worms
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
Helios Klinikum Wuppertal
Wuppertal
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Providence Medical Foundation
92835 Fullerton
United StatesRekrutierend» Google-Maps
California Research Institute
90027 Los Angeles
United StatesRekrutierend» Google-Maps
Dana-Farber Cancer Institute
02215 Boston
United StatesRekrutierend» Google-Maps
Miami Valley Hospital South
45459 Centerville
United StatesRekrutierend» Google-Maps
SCRI Oncology Partners
37203 Nashville
United StatesRekrutierend» Google-Maps
University of Texas MD Anderson Cancer Center
77030 Houston
United StatesRekrutierend» Google-Maps
UT Health San Antonio University of Texas
78229 San Antonio
United StatesNoch nicht rekrutierend» Google-Maps
Virginia Cancer Institute
00115 Norfolk
United StatesNoch nicht rekrutierend» Google-Maps
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
Leuven
BelgiumRekrutierend» Google-Maps
Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc
Woluwe-Saint-Lambert
BelgiumRekrutierend» Google-Maps
Hôpital Morvan - CHRU de Brest - cancérologie et d'hématologie
Brest
FranceRekrutierend» Google-Maps
Centre de Cancerologie du Grand Montpellier
37070 Montpellier
FranceRekrutierend» Google-Maps
Hôpital de la Pitiê Salpêtriêre
75103 Paris
FranceRekrutierend» Google-Maps
Centre Hospitalier Universitaire de Poitiers
86000 Poitiers
FranceRekrutierend» Google-Maps
National and Capodistrian University of Athens - University General Hospital Attikon
12462 Athens
GreeceRekrutierend» Google-Maps
Metropolitan Hospital [Oncology]
12462 Piraeus
GreeceRekrutierend» Google-Maps
EUROMEDICA General Clinic of Thessaloniki
54645 Thessaloníki
GreeceRekrutierend» Google-Maps
Interbalkan European Medical Center
57001 Thessaloníki
GreeceRekrutierend» Google-Maps
AOU Ospedali Riuniti Umberto I-G.M.Lancisi -G.Salesi
Ancona
ItalyRekrutierend» Google-Maps
IEO - Istituto Europeo di Oncologia, IRCCS
Milano
ItalyRekrutierend» Google-Maps
Ospedale San Gerardo, ASST di Monza, IRCCS
Monza
ItalyRekrutierend» Google-Maps
Azienda Ospedaliera Santa Maria di Terni
Terni
ItalyRekrutierend» Google-Maps
Asan Medical Center
05505 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Gangnam Severance Hospital
06273 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Samsung Medical Center
06351 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Ewha Womans University MokDong Hospital
07985 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Seoul National University Bundang Hospital
Seoul
Korea, Republic ofRekrutierend» Google-Maps
Seoul National University Hospital
Seoul
Korea, Republic ofRekrutierend» Google-Maps
University Hospital Reina Sofía
14004 Córdoba
SpainRekrutierend» Google-Maps
University Hospital Ramón y Cajal
28034 Madrid
SpainRekrutierend» Google-Maps
University Hospital 12 de Octubre
28041 Madrid
SpainRekrutierend» Google-Maps
Clara Campal Comprehensive Cancer Center (CIOCC)
28050 Madrid
SpainRekrutierend» Google-Maps
University Clinical Hospital Virgen de la Arrixaca
30120 El Palmar
SpainRekrutierend» Google-Maps
Hospital Clinic De Barcelona
08036 Barcelona
SpainRekrutierend» Google-Maps
Hospital Universitario Quirónsalud Madrid
Madrid
SpainRekrutierend» Google-Maps
Complexo Hospitalario Universitario De Santiago
15706 Santiago De Compostela
SpainRekrutierend» Google-Maps
Ankara Bilkent Sehir Hastanesi Tibbi Onkoloji Klinigi
Ankara
TurkeyRekrutierend» Google-Maps
Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
Ankara
TurkeyRekrutierend» Google-Maps
Gulhane Egitim ve Arastirma Hastanesi Tibbi Onkoloji Klinigi
Ankara
TurkeyRekrutierend» Google-Maps
Hacettepe University Medical Faculty
Ankara
TurkeyRekrutierend» Google-Maps
Memorial Ankara Hastanesi Tibbi Onkoloji
Ankara
TurkeyRekrutierend» Google-Maps
Prof. Dr. Suleyman Yalcin Sehir Hastanesi
Istanbul
TurkeyRekrutierend» Google-Maps
University Hosiptals of Leicester NHS Trust -Glenfield Hospital
Leicester
United KingdomNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Anu Palathingal
Phone: 44 116 258 6687
E-Mail: anu.palathingal@uhl-tr.nhs.uk» Ansprechpartner anzeigen
Guy's and St Thomas' NHS Foundation Trust
London
United KingdomRekrutierend» Google-Maps
Ansprechpartner:
Ellie McDowall
Phone: 44 207 188 7188
Phone (ext.): 51783
E-Mail: Ellie.mcdowall@gstt.nhs.uk» Ansprechpartner anzeigen
University College London Hospitals NHS Foundation Trust - University College Hospital (UCH) - Macmillan Cancer Centre
London
United KingdomRekrutierend» Google-Maps
Ansprechpartner:
Ioannis Charalampidis
Phone: 44 203 447 2929
E-Mail: ioannis.charalampidis@nhs.net» Ansprechpartner anzeigen
The Christie NHS Foundation Trust - Medical Oncology
M20 4BX Manchester
United KingdomRekrutierend» Google-Maps
Ansprechpartner:
Zoe Brammer
Phone: 44 161 446 8347
E-Mail: zoe.brammer@nhs.net


Phone: 44 161 918 2352» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Brief Summary:

This is a multi-site, global, open-label study that includes a phase 1b evaluation of

elacestrant in combination with abemaciclib in women and men with brain metastases from

estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER-2)

negative breast cancer. Phase 1b was designed to select the recommended phase 2 dose and

is followed by an ongoing phase 2 evaluation of elacestrant in combination with

abemaciclib in patients with active brain metastases from ER-positive, HER-2 negative

breast cancer.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Patient has the signed informed consent form before any study-related activities

according to local guidelines.

2. Women or men aged ≥18 years, at the time of informed consent signature.

- Female patients may be either postmenopausal or pre/perimenopausal.

Postmenopausal status is defined by:

1. Age ≥60 years

2. Age <60 years and amenorrhea for 12 or more months without an alternative

cause) and follicle stimulating hormone and estradiol in postmenopausal

ranges per local reference ranges

3. Documentation of prior bilateral oophorectomy, at least 1 month before

first dose of trial therapy).

3. Patient must have ER-positive, HER-2 negative tumor status as confirmed by local

laboratory testing in the following manner:

- Documentation of ER positive tumor with ≥ 1% staining by immunohistochemistry

(IHC) as defined in the 2010 or 2020 American Society for Clinical Oncology

(ASCO) recommendations for ER testing, with or without progesterone receptor

(PGR) positivity

- HER-2 negative tumor with an IHC result of 0 or 1+ for cellular membrane

protein expression or an in situ hybridization negative result as defined in

the 2013 or 2018 ASCO recommendations for HER-2 testing

4. In Phase 2, patients must have at least one active and measurable brain metastasis

per RECIST version 1.1.

- Any of the following qualifies brain metastases as active:

1. Newly diagnosed brain metastasis in patients who never received prior

central nervous system (CNS)-directed therapy.

2. Newly diagnosed brain metastasis outside any area that was previously

subjected to CNS-directed therapy.

3. Brain metastases that are clearly progressing in an area that has

previously been subjected to CNS-directed therapy.

- For lesions, including brain metastases, to qualify as measurable, and possibly

be selected as target lesions, per RECIST version 1.1 (Appendix C), the longest

diameter must be ≥10 mm by CT or MRI).

- In Phase 1b, the presence of brain metastases is allowed but not required for

eligibility, in this case, at least 1 measurable lesion outside the brain is

required.

5. Patients receiving concomitant corticosteroids must be on a stable or decreasing

dose for at least 7 days prior to baseline and not receiving doses higher than 4 mg

of dexamethasone per day or equivalent.

6. Any neurological symptoms of brain metastases must be stable for at least 2 weeks

before starting trial therapy. Fluctuations of the previously known symptoms deemed

to be due to clinical intercurrent processes (e.g., electrolytes alterations, fever)

are admissible if fully resolved before the first dose of study drugs.

7. Patient prior therapy received in the metastatic setting includes:

- At least one endocrine therapy

- Up to two chemotherapy regimens

- Up to two prior CDK 4/6 inhibitors, not including abemaciclib Note 1: Toxicity

from prior therapy must be resolved to National Cancer Institute (NCI) CTCAE

version 5.0 Grade ≤1, with the exception of alopecia and peripheral sensory

neuropathy (Grade ≤2).

8. Patient has documented intra- and/or extra-cranial radiological progression or

recurrence while on or after the most recent therapy.

9. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

10. Patient has adequate bone marrow and organ function, as defined by the following

laboratory values:

1. Absolute neutrophil count (ANC) ≥1.5 × 109/L

2. Platelets ≥100 × 109/L

3. Hemoglobin ≥9.0 g/dL

4. Potassium, sodium, calcium (corrected for serum albumin) and magnesium CTCAE

Grade ≤1 (if screening assessments are abnormal, these assessments may be

repeated up to 2 times; subjects may receive appropriate supplementation or

treatment prior to reassessment)

5. Creatinine clearance (per Cockcroft-Gault formula) ≥50 mL/min

6. Serum albumin ≥3.0 g/dL (≥30 g/L)

7. Liver function tests:

In absence of liver metastases, alanine aminotransferase (ALT) and aspartate

aminotransferase (AST) ≤3.0 × upper limit of normal (ULN). If the patient has

liver metastases, ALT and AST ≤5 × ULN.

8. Total serum bilirubin <1.5 × ULN except for patients with Gilbert's syndrome

who may be included if the total serum bilirubin is ≤3.0 × ULN or direct

bilirubin ≤ 1.5 × ULN

11. The patient is willing and able to adhere to the study visit schedule and other

protocol requirements.

Exclusion Criteria:

1. Immediate CNS-specific treatment is likely to be required, per the treating

physician's assessment.

2. Patient has imminent organ failure and/or visceral crisis.

3. Patient has leptomeningeal metastases, defined as having positive CSF cytology or

unequivocal radiologic and clinical evidence of leptomeningeal involvement.

4. Breast cancer treatment-naïve patients in the advanced/metastatic setting.

5. Prior therapy with abemaciclib in the metastatic setting. Note: Use of abemaciclib

in the adjuvant setting is allowed if the last treatment administration was more

than 12 months prior to first recurrence.

6. Prior therapy with elacestrant or other investigational SERDs, or investigational

alike agents such as SERMs, SERCANs, CERANs, and PROTACs in the metastatic setting.

7. Patient has a concurrent malignancy or malignancy within 3 years of enrollment, with

the exception of adequately treated basal or squamous cell skin cancer, superficial

bladder cancer, carcinoma in situ of the cervix, or second primary breast cancer.

8. Currently participating in another breast cancer intervention clinical study.

Patients who are being followed for overall survival for another clinical trial with

no therapy and study intervention are allowed after the washout period for any prior

therapy.

9. Prior anti-cancer or investigational drug treatment within the following windows:

- Fulvestrant treatment (last injection) <42 days before first dose of study drug

- Any other endocrine therapy <14 days before first dose of study drug. Note:

LHRH agonists should not be counted as endocrine therapy.

- Chemotherapy or other anti-cancer therapy <14 days before first dose of study

drug

- Any investigational anti-cancer drug therapy within <28 days or <5 half lives,

whichever is shorter

- Bisphosphonates or RANKL inhibitors initiated, or dose changed <1 month prior

to first dose of study drug.

10. Radiation therapy (other than CNS directed) within 14 days before the first dose of

study drug. CNS directed radiation therapy within 28 days before the first dose of

study drug.

11. Uncontrolled significant active infections

- Patients with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection

must have undetectable viral load during screening

- Patients known to be HIV+ are allowed as long as they have undetectable viral

load at baseline.

12. Major surgery within 4 weeks of starting trial therapy.

13. Inability to take oral medication, or history of malabsorption syndrome or any other

uncontrolled gastrointestinal condition.

14. Females of childbearing potential who do not agree to use a highly effective

non-hormonal method of contracept

ion and to abstain from donating ova within 28 days of the first dose of study

treatment through 120 days after the last dose of study treatment. Highly effective

non-hormonal method of contraception includes any of the following:

1. Intrauterine device (non-hormonal)

2. Sexual abstinence

3. Bilateral tubal occlusion/ligation

4. Have a vasectomized partner with confirmed azoospermia.

15. Male patients (including males with a vasectomy) with a pregnant or non-pregnant

female of childbearing potential partner who do not agree to use a highly effective

barrier contraception method (condoms) within 28 days ofthe first dose of study

treatment until 120 days of the last dose of study treatment. And male patients who

do not agree to abstain from donating sperm within the same period. In addition,

female partners of childbearing potential, of male patients (who has not undergone

vasectomy) must use highly effective methods of contraception.

16. Females who are pregnant or breastfeeding. Females should not get pregnant during

study treatment and for 120 days after last dose of study treatment. Females should

not breastfeed during administration of elacestrant and for 1 week after receiving

the last dose.

17. Known intolerance to either study drug or any of the excipients.

18. Patients currently receiving or received any of the following medications prior to

first dose of trial therapy:

1. Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4

(including foods and herbal preparations) within 14 days or <5 half-lives,

whichever is shorter)

2. Herbal preparations/medications (which are not strong or moderate inducers or

inhibitors of CYP3A4). These include, but are not limited to , kava, ephedra

(ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw

palmetto, and ginseng within 7 days prior to initiating trial therapy

3. Vaccination, including but not limited to vaccination against COVID-19, during

the 7 days prior to randomization.

19. Any severe medical or psychiatric condition that in the opinion of the

investigator(s) would preclude the patient's participation in a clinical study.

Studien-Rationale

Primary outcome:

1. Recommended phase 2 dose (RP2D) (Time Frame - 1 year):
Based on the observed number of dose-limiting toxicities (DLTs) during the first cycle. Dose-limiting toxicity is based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. DLTs will be evaluated during the first cycle (28 days) of treatment in up to 3 cohorts during Phase 1b. A DLT will be defined as any of the toxicities listed in the protocol that are not clearly due to breast cancer or extraneous causes.

2. Objective Response Rate (ORR) (Time Frame - 3 years):
Defined as the proportion of patients with a best overall response (BOR) of either a complete response or partial response per blinded independent central review, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

Secondary outcome:

1. Intracranial Response Rate (RR) per RECIST v1.1 (Time Frame - 3 years):
Defined as the proportion of patients achieving a best overall response of confirmed partial response + complete response, based on intracranial lesions per RECIST v1.1 and blinded independent central review.

2. Intracranial RR per Response Assessment in Neuro-Oncology (RANO) (Time Frame - 3 years):
Defined as the proportion of patients achieving a best overall response of confirmed partial response plus complete response, based on intracranial lesions (per RANO criteria) and per blinded independent central review.

3. Duration of Tumor Response (DOR) (Time Frame - 3 years):
Defined as the duration of time from the date when criteria are met for either a complete response or partial response, per RECIST v1.1, until the first date that progressive disease is objectively documented, per blinded independent central review.

4. Clinical Benefit Rate (CBR) (Time Frame - 3 years):
Defined as the proportion of patients who have the best overall response a complete response, a partial response, or stable disease.

5. Progression-Free Survival (PFS) (Time Frame - 3 years):
Defined as the time elapsing between the start of treatment and the date of the earliest evidence of objective disease progression or death of any cause before documented disease-progression assessed through study completion.

Studien-Arme

  • Experimental: Phase 1b Cohort 1
    Elacestrant 300 mg once daily (QD) + abemaciclib 100 mg twice daily (BID)
  • Experimental: Phase 1b Cohort 2
    Elacestrant 400 mg QD + abemaciclib 100 mg BID
  • Experimental: Phase 1b Cohort 3
    Elacestrant 400 mg QD + abemaciclib 150 mg BID
  • Experimental: Phase 2
    Elacestrant in combination with abemaciclib at the recommended phase 2 dose (RP2D) determined in phase 1b

Geprüfte Regime

  • Elacestrant (Elacestrant dihydrochloride / RAD-1901 / ER-306323 / Orserdu / ):
    300 mg, 400 mg
  • Abemaciclib (Verzenio):
    100 mg, 150 mg

Quelle: ClinicalTrials.gov


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"Study of Abemaciclib and Elacestrant in Patients With Brain Metastasis Due to ER+/HER-2- Breast Cancer"

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